The proposed research is aimed at (1) the development of a radionuclide generator system for ionic gallium-68 using column chromatography (ion exchange or adsorption chromatography), and (2) the labeling of biologically active proteins with gallium-68 via chelation to a DTPA moiety covalently bound to the protein. The generator should be simple to manipulate, be capable of at least 600 elutions, and reproducibly deliver carrier-free ionic Ga-68 without Ge-68 contamination (breakthrough) in less than 10ml of physiologically acceptable eluate. The chromatographic systems to be explored are based on an inorganic absorbent (alumina) and on an organic substrate (pyrogallol-formaldehyde resin). Stress will be laid on the yield of gallium-68 and the purity of the eluates from both the chemical and radiochemical standpoint. Distribution coefficients between the various substrates and eluates will be determined and experimental generators of increasing activity will be built. Toxicity studies will be carried out in two animal species using the products of chemically attractive generator systems. Concomitantly, there is an immediate need for a simple and effective method of linking a strongly chelating molecule to proteins of medical interest such that the chelated radionuclide (gallium-68 in this instance) is stable in a serum environment and that the radiolabeled protein retains its original biochemical activity. To this end the labeling of proteins with DTPA via an amide linkage through one of the DTPA carboxyl groups will be investigated. The reaction sequence involves the preparation of the anhydride of DTPA and subsequent reaction with a free amine group on the protein to form the covalent amide linkage.